Coenzyme Q is a naturally-occurring enzyme cofactor found in the mitochondria of the body cells.
Several types of coenzyme Q have been identified and numbered from zero upwards. The variety found in human tissue is coenzyme Q10 (ubiquinone) and so is the term used here.
Coenzyme Q10 has the following functions:
It is involved in electron transport and supports the synthesis of adenosine triphosphate (ATP) in the mitochondrial membrane.
It plays a vital role in intracellular energy production.
It is a fat-soluble antioxidant that helps to stabilise cell membranes, preserving cellular integrity and function. It also helps to regenerate vitamin E to its antioxidant form.
It is essential for normal myocardial function. It has immunostimulant activity.
It may be obtained from the diet or a food supplement, but it is also produced endogenously.
Meat and fatty fish products are the most concentrated sources, although smaller quantities are found in wholegrain cereals, soya beans, nuts and vegetables, particularly spinach and broccoli. The relative importance of endogenous synthesis and dietary intake to coenzyme Q10 status has not been established. Coenzyme Q10 is also found in a number of food supplements, either as the sole active ingredient or in combination with vitamins and/or minerals, especially magnesium.
Absorption of coenzyme Q10 from the diet or a supplement occurs in the small intestine and is influenced by the presence of food and drink. It is better absorbed in the presence of a fatty meal. After absorption, it is transported to the liver where it is incorporated into lipoproteins and bound principally to VLDL and LDL cholesterol. It is then concentrated in the tissues. One study found that coenzyme Q10 from both foods and supplements significantly raised serum concentrations.
Coenzyme Q10 is produced endogenously from tyrosine within all cells of the body, but specifically in the heart, liver, kidney and pancreas, where it plays an indispensable role in intracellular energy production. Several cofactors are involved in its synthesis, including riboflavin, pyridoxine, folic acid, vitamin B12, niacin, pantothenic acid and vitamin C. The ability to synthesise coenzyme Q10 decreases as people get older. The concentration of coenzyme Q10 in human tissue appears to be related to age, peaking at age 20 and declining after that.
Because coenzyme Q10 is not an essential nutrient in the same way as a vitamin or mineral, no Dietary Reference Values or RDAs have been established. However, there is increasing speculation based on serum and/or biopsy samples that certain signs and symptoms are associated with a lack of coenzyme Q10.
Whether the observed lack of coenzyme Q10 in these conditions is a true deficiency that contributes to the development of the disease or is caused by the disease itself is unclear. In heart failure, those with the most advanced disease have lower coenzyme Q10 levels than those with less advanced disease.9 Low serum coenzyme Q10 levels are also associated with a significant risk of heart failure or increased mortality.
Deficiency may occur as a result of:
Inadequate intake or production, particularly if requirements are increased because of disease.
Inadequate production caused by older age or by deficiencies of nutrients required for its synthesis.
Genetic or acquired defects in synthesis or metabolism.
Interactions with medicines
Beta-blockers, clonidine, gemfibrozil, hydralazine, hydro-chlorothiazide, methyldopa, statins and tricyclic antidepressants may reduce levels of coenzyme Q10.
The potential role of coenzyme Q10 in CVD has been studied over more than 30 years. Studies increasingly look at its role in specific cardiovascular conditions but an open study in 424 patients published in 1994 indicated that coenzyme Q10 supplementation may have benefits in cardiac function in patients with a range of cardiovascular disorders, including ischaemic cardiomyopathy, dilated cardio-myopathy, primary diastolic dysfunction, hypertension, valvular heart disease and mitral valve prolapse.
Congestive heart failure
There is substantive evidence suggesting a role for coenzyme Q10 in CHF. Oxidative stress is believed to play a role in the aetiology of CHF. It has been suggested that low coenzyme Q10 levels found in patients with CHF contribute to the disease while supplementation with prepa-rations that include coenzyme Q10 may produce an improvement.
A double-blind, placebo-controlled study investigated 322 patients with CHF who were randomly assigned to receive 2 mg coenzyme Q10/kg daily or a placebo for 1 year. The number of episodes of pulmonary oedema or cardiac asthma was significantly fewer in the intervention group than the placebo group. The supplemented patients also had fewer hospitalisations. A meta-analysis of eight clin-ical trials of coenzyme Q10 in patients with CHF found that supplemental treatment of CHF was significant, with significant improvement in stroke volume, ejection fraction, cardiac output, cardiac index and diastolic volume index.
Not all clinical trials have produced positive results. In a double-blind, placebo-controlled, crossover study, 30 patients with chronic left ventricular dysfunction were randomised to receive coenzyme Q10 or a placebo for 3 months each. Plasma levels of coenzyme Q10 increased to more than twice baseline values, but there were no significant differences between treatments in left ventricular ejection fraction, cardiac volumes, haemodynamic indices or quality of life measures. In another RCT, 55 patients with CHF were randomly assigned to receive 200 mg coenzyme Q10 or a placebo daily for 6 months. Patients receiving the supplement had higher serum concentrations of coenzyme Q10, but there were no differences in cardiac performance, peak oxygen consumption and exercise duration between the treated group and the placebo group.
Coenzyme Q10 levels tend to be low in patients with ischaemic heart disease and several clinical trials have been conducted in patients with angina. Overall, coenzyme Q10 appears to delay onset of angina and increases patients’ stamina on a treadmill. In one RCT, 144 patients with acute myocardial infarction were given 120 mg coenzyme Q10 or a placebo daily for 28 days, starting within 3 days of the heart attack. There was a significant improvement in angina pectoris, total arrhythmias and poor left ventricular function in the intervention group. Total cardiac events, including cardiac deaths and non-fatal infarction were also significantly lower in the supplemented group than the placebo group.
Coenzyme Q10 has been investigated for hypertension both as a stand-alone treatment and as an adjunct to conventional antihypertensive medication. In one randomised double-blind study involving 83 patients, an oral dose of 60 mg taken twice a day over 12 weeks was found to produce a mean reduction in systolic blood pressure of 17.8 ± 7.3 mmHg. Another double-blind study in 59 patients with hypertension found that adding 120 mg coenzyme Q10 daily to existing anti-hypertensive medication causes an additional reduction in systolic and diastolic blood pressure after 8 weeks’ treatment.
Studies have looked at the use of coenzyme Q10 supplements before cardiac surgery. Oral supplementation with coenzyme Q10 for 2 weeks before cardiac surgery has been shown to improve post-operative heart function and shorten hospital stays. However, supplementation with 600 mg coenzyme Q10 12 h before surgery did not improve myocardial protection in patients undergoing coronary revascularisation.
Coenzyme Q10 is essential in energy metabolism and has therefore been investigated for athletic performance. Controlled trials using doses of 60–150 mg daily over 28 days to 8 weeks have generally shown no improvements in physical performance. However, in one double-blind crossover trial, there were positive results on both objective and subjective parameters of physical performance. In this study, 94% of athletes felt that coenzyme Q10 improved their performance and recovery times compared with 33% taking a placebo.
Studies suggest that oxidative damage, inflammation and mitochondrial impairment may play a role in the aetiology of Parkinson’s disease. In a multicentre, randomised, placebo-controlled, double-blind study comparing three different doses of coenzyme Q10 (300, 600, and 1200 mg) in 80 patients with early Parkinson’s disease, significant improvements were reported after 9 months in the group taking 1200 mg daily.
A randomised double-blind study involving 347 patients with early Huntington’s chorea showed that a dose of coenzyme Q10 600 mg daily taken over 30 months produced a trend towards slow decline and beneficial improvements in some parameters. However, changes were not significant.
Observational studies of women diagnosed with breast cancer have reported reduced blood coenzyme Q10 concentrations. There have also been several case reports of remissions or partial remissions in patients with tumours. However, there are no controlled studies to show the effectiveness of coenzyme Q10 in cancer.
An open trial investigated the effects of coenzyme Q10 150 mg daily for 3 months in 32 individuals with a history of migraine. Coenzyme Q10 was associated with a significant reduction in both the frequency of attacks and the number of days with migraine.
Pregnancy and breast-feeding
Safety in pregnancy has not been established.
Coenzyme Q10 seems to be safe and relatively well tolerated in doses of 10–200 mg daily. There are occasional reports of gastrointestinal discomfort, dizziness and skin rash, but these tend to occur with doses > 200 mg daily.
Statins: Simvastatin, pravastatin and lovastatin reduce endogenous synthesis of coenzyme Q10.6 The mechanism of action of statins is inhibition of HMG-CoA reductase. Inhibition of this enzyme appears to inhibit the intrinsic biosynthesis of coenzyme Q10 at the same time. This reduces coenzyme Q10 concentrations, so constituting a new risk for CVD. Supplementation may increase levels without adversely affecting drug efficacy.
Warfarin: Case reports suggest that coenzyme Q10 may decrease international normalised ratio (INR) in patients previously stabilised on anti-coagulants. However, a double-blind crossover study in 24 patients on long-term warfarin found that oral coenzyme Q10 100 mg daily had no significant effect on INR or warfarin levels.26 In patients on warfarin, high doses of coenzyme Q10 should be used with caution.
Coenzyme Q10 should not be used to treat cardiovascular disorders without medical supervision.
Coenzyme Q10 is sold in capsules and tablets in strengths of 10–150 mg. Doses used in studies investigating CVD and prevention of migraine have ranged from 100 to 150 mg daily. How-ever, higher doses have been used in angina (150–600 mg daily) and Parkinson’s disease (up to 1200 mg daily). Doses used to prepare for heart surgery have varied between 30 and 100 mg daily for 1–2 weeks before surgery and a month afterwards.
People who wish to try coenzyme Q10 for cardiovascular conditions or migraine prevention should be advised it may take 10–12 weeks to have an effect. However all patients with cardiovascular conditions should take medical advice before taking coenzyme Q10.
Results from preliminary studies with co-enzyme Q10 suggest that it may help improve symptoms of CHF, and may help to protect against myocardial infarction. Studies in angina and hypertension are inconclusive. Studies conducted so far do not justify the use of coenzyme Q10 in cancer, athletes and sports people and AIDS, though some of the preliminary research justifies more rigorous trials to investigate potential benefits. Preliminary evidence from the use of coenzyme Q10 in Parkinson’s disease is promising. However, there is insufficient evidence to make definite recommendations for coenzyme Q10 as a dietary supplement.
Dietary Supplements, Third Edition, by Pamela Mason, BSc, MSc, PhD, MRPharmS, published by Pharmaceutical Press, London, 2007.
Weber C, Bysted A, Holmer G. Coenzyme Q10 in the diet – daily intake and relative bioavailability. Mol Aspects Med 1997; 18: S251–S254.
Kalen A, Appelkvist EL, Dallner G. Age-related changes in the lipid composition of rat and human tissue. Lipids 1989; 24: 579–584.
Sole MJ, Jeejeebhoy KN. Conditioned nutritional requirements: therapeutic relevance to heart failure. Herz 2002; 27: 174–178.
Karlsson J, Diamant B, Folkers K, Lund B. Muscle fibre types, ubiquinone content and exercise capacity in hypertension and effort angina. Ann Med 1991; 23: 339–344.
Mortensen SA, Vadhanavikit S, Muratsu K, Folkers K. Coenzyme Q10: clinical benefits with biochemical correlates suggesting a scientific breakthrough in the management of chronic heart failure. Int J Tissue React 1990; 12: 155–162.
Overvard K, Diamant B, Holm L, et al. Coenzyme Q10 in health and disease. Eur J Clin Nutr 1999; 53: 764–770.
Bianchi G, Solaroli E, Zaccheroni V, et al. Oxidative stress and antioxidant metabolites in patients with hyperthyroidism: effect of treatment. Horm Metab Res 1999; 31: 620–624.
Folkers K, Osterborg A, Nylander M, et al. Activities of vitamin Q10 in animal models and a serious deficiency in patients with cancer. Biochem Biophys Res Commun 1997; 234: 296–299.
Mortensen SA. Perspectives on therapy of cardio-vascular diseases with coenzyme Q (ubiquinone). Clin Investig 1993; 71: S116–S123.
Jameson S. Statistical data support prediction of death within 6 months on low levels of coenzyme Q10 and other entities. Clin Investig 1993; 71: S137–S139.
Langsjoen H, Langsjoen P, Langsjoen P, et al. Usefulness of coenzyme Q10 in clinical cardiology: a long term study. Mol Aspects Med 1994; 15 (Suppl.): S165–S175.
Morisco C, Trimarco B, Condorelli M. Effect of coenzyme Q10 therapy in patients with conges-tive heart failure: a long term multicenter randomized study. Clin Investig 1993; 71: S134–S136.
Soja AM, Mortensen SA. Treatment of congestive heart failure with coenzyme Q10 illustrated by meta-analyses of clinical trials. Mol Aspects Med 1997; 18: S159–S168.
Watson PS, Scalia GM, Galbraith A, et al. Lack of effect of coenzyme Q on left ventricular function in patients with congestive heart failure. J Am Coll Cardiol 1999; 33: 1549–1552.
Khatta M, Alexander BS, Krichten CM, et al. The effect of coenzyme Q10 with congestive heart failure. Ann Intern Med 2000; 132: 636–640.
Singh RB, Wander GS, Rastogi A, et al. Ran-domized, double-blind, placebo-controlled trial of coenzyme Q10 in patients with acute myocardial infarction. Cardiovasc Drugs Ther 1998; 12: 347– 353.
Burke BE, Neuenschwander R, Olson RD. Ran-domized, double-blind, placebo-controlled trial of coenzyme Q10 in isolated systolic hypertension.
South Med J 2001; 94: 1112–1117.
Singh RB, Niaz MA, Rastogi SS, et al. Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance in hypertensive patients with coronary artery disease. J Hum Hypertens 1999; 13: 203–208.
Rosenfeldt FL, Pepe S, Linnane A, et al. The effects of ageing on the response to cardiac surgery: protective strategies for the ageing myocardium. Biogerontology 2002; 3: 37–40.
Taggart DP, Jenkins M, Hooper J, et al. Effects of short term supplementation with coenzyme Q10 on myocardial protection during cardiac operations. Ann Thorac Surg 1996; 61: 829–833.
Ylikoski T, Piirainen J, Hanninen O, Penttinen J. The effect of coenzyme Q10 on the exercise performance of cross-country skiers. Mol Aspects Med 1997; 18: S283–S290.
Ebadi M, Govitrapong P, Sharma S, et al. Ubiquinone (coenzyme Q10) and mitochondria in oxidative stress in Parkinson’s disease. Biol Signals Recept 2001; 10: 224–253.
Shults CW, Oakes D, Kieburtz K, et al. Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol 2002; 59: 1541–1550.
Huntington’s Study Group. A randomized, placebo-controlled trial of coenzyme Q10 and remacemide in Huntington’s disease. Neurology 2001; 57: 397–404.
Rozen TD, Oshinsky ML, Gebeline CA, et al. Open label trial of coenzyme Q10 as a migraine preventive.Cephalgia 2002; 22: 137–141.
Engelson J, Nielson JD, Hansen KF. Effect of coenzyme Q10 and ginkgo biloba on war-farin dosage in patients on long-term warfarin treatment. A randomized, double-blind, placebo-controlled crossover trial. Ugeskr Laeger 2003; 165: 1868–1871.